{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T08:55:00Z","timestamp":1791881700865,"version":"4.3.4"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    B\u2010cell acute lymphoblastic leukemia (B\u2010ALL) is a heterogeneous malignancy driven by diverse genetic alterations. Among these,\n                    <jats:italic>CEBP<\/jats:italic>\n                    family genes and\n                    <jats:italic>ZEB2<\/jats:italic>\n                    are recurrently involved, yet the spectrum of genomic mechanisms and their clinical impact remain incompletely defined. Integrated genomic analyses of a cohort of 992 Philadelphia\u2010negative adult B\u2010ALL patients revealed multiple mechanisms of enhancer hijacking\u2010mediated deregulation of\n                    <jats:italic>CEBPA<\/jats:italic>\n                    ,\n                    <jats:italic>CEBPB<\/jats:italic>\n                    ,\n                    <jats:italic>CEBPD<\/jats:italic>\n                    , and\n                    <jats:italic>CEBPE<\/jats:italic>\n                    , including\n                    <jats:italic>IGH<\/jats:italic>\n                    and several non\u2010\n                    <jats:italic>IGH<\/jats:italic>\n                    fusions, as well as noncoding mutations in regulatory regions. Combined with gene expression analysis, we identified three distinct subtypes, defined by co\u2010occurring\n                    <jats:italic>CEBP<\/jats:italic>\n                    and\n                    <jats:italic>ZEB2<\/jats:italic>\n                    p.H1038R alterations (CEBP\/ZEB2,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200918 cases); isolated\n                    <jats:italic>CEBP<\/jats:italic>\n                    alterations (CEBPalt,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200943), associated with frequent\n                    <jats:italic>IKZF1<\/jats:italic>\n                    deletions and\n                    <jats:italic>FLT3<\/jats:italic>\n                    deregulation; and isolated\n                    <jats:italic>ZEB2<\/jats:italic>\n                    p.H1038R mutation (ZEB2alt,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915), associated with various additional genomic hits targeting\n                    <jats:italic>ZEB2<\/jats:italic>\n                    and enhancing mutant\n                    <jats:italic>ZEB2<\/jats:italic>\n                    expression. The three subtypes exhibited distinct clinical features, including age distribution (patients with CEBP\/ZEB2 and ZEB2alt B\u2010ALL were younger) and sex bias (female and male predominance in CEBPalt and ZEB2alt, respectively). Early treatment responses and outcomes also differed: patients with CEBP\/ZEB2 B\u2010ALL had a favorable early response, in contrast to patients with ZEB2alt B\u2010ALL, who had high levels of minimal residual disease and a dismal prognosis. Collectively, our findings define\n                    <jats:italic>CEBP<\/jats:italic>\n                    and\n                    <jats:italic>ZEB2<\/jats:italic>\n                    alterations as drivers of genetically and clinically distinct subtypes of adult B\u2010ALL and provide a rationale for subtype\u2010specific risk stratification. Preclinical experiments in CEBPalt B\u2010ALL patient\u2010derived xenografts demonstrated sensitivity to FLT3 inhibition, highlighting a potential therapeutic vulnerability.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70383","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:15:17Z","timestamp":1781514917000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>CEBP<\/i>\n                    and\n                    <i>ZEB2<\/i>\n                    alterations define three distinct subtypes of B\u2010cell acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9987-7237","authenticated-orcid":false,"given":"Rathana","family":"Kim","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm UMR 1342, Institut de Recherche Saint\u2010Louis (IRSL) Paris France"},{"name":"Laboratoire d'H\u00e9matologie AP\u2010HP, h\u00f4pital Saint\u2010Louis Paris France"},{"name":"The Leukemia Institute Paris Saint\u2010Louis Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Passet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm UMR 1342, Institut de Recherche Saint\u2010Louis (IRSL) Paris France"},{"name":"Laboratoire d'H\u00e9matologie AP\u2010HP, h\u00f4pital Saint\u2010Louis Paris France"},{"name":"The Leukemia Institute Paris Saint\u2010Louis Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Bergugnat","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm UMR 1342, Institut de Recherche Saint\u2010Louis (IRSL) Paris France"},{"name":"The Leukemia Institute Paris Saint\u2010Louis Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9065-0477","authenticated-orcid":false,"given":"Lo\u00efc","family":"Vasseur","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm UMR 1342, Institut de Recherche Saint\u2010Louis (IRSL) Paris France"},{"name":"The Leukemia Institute Paris Saint\u2010Louis Paris France"},{"name":"Service d'H\u00e9matologie AP\u2010HP, h\u00f4pital Saint\u2010Louis Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Leguay","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie CHU de Bordeaux, h\u00f4pital du Haut\u2010Lev\u00eaque Pessac France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Huguet","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie Institut Universitaire de Cancer Toulouse\u2010Oncopole, CHU de Toulouse Toulouse 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